On September 15, 2023 Daiichi Sankyo (TSE: 4568) reported that quizartinib has been recommended for approval in the European Union (EU) in combination with standard cytarabine and anthracycline induction and standard cytarabine consolidation chemotherapy, followed by quizartinib single-agent maintenance therapy, for adult patients with newly diagnosed acute myeloid leukemia (AML) that is FLT3-ITD positive (Press release, Daiichi Sankyo, SEP 15, 2023, View Source [SID1234635188]).

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The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based its positive opinion on results from the phase 3 QuANTUM-First trial, which were published in The Lancet. The recommendation will now be reviewed by the European Commission, which has the authority to grant marketing authorizations for medicines in the EU.

In QuANTUM-First, quizartinib combined with standard cytarabine and anthracycline induction and standard cytarabine consolidation, and continued as maintenance monotherapy following consolidation, demonstrated a 22% reduction in the risk of death compared to standard chemotherapy alone (HR = 0.78 [95% CI: 0.62-0.98; p=0.032]) in patients with newly diagnosed FLT3-ITD positive AML. Median overall survival was 31.9 months for patients receiving quizartinib (n=268; 95% CI: 21.0-NE) compared to 15.1 months for patients in the control arm (n=271; 95% CI: 13.2-26.2) at a median follow-up of 39.2 months.

"Today’s positive CHMP opinion for quizartinib is an important step towards translating the clinical benefit observed in QuANTUM-First into an approved treatment option for patients in the EU with the difficult-to-treat FLT3-ITD subtype of acute myeloid leukemia," said Mark Rutstein, MD, Global Head, Oncology Clinical Development, Daiichi Sankyo. "If approved, quizartinib would be the first FLT3 inhibitor approved specifically for patients with newly diagnosed FLT3-ITD positive AML."

The safety profile of quizartinib in QuANTUM-First was consistent with previous clinical trials with no new safety signals observed. The most common grade 3 or 4 treatment emergent adverse events (occurring in ≥ 10% of patients) were febrile neutropenia (43%), hypokalemia (19%), neutropenia (18%) and pneumonia (11%). QTcF > 500 ms occurred in 2.3% of patients receiving quizartinib and 0.8% of patients discontinued quizartinib due to QT prolongation. Ventricular arrhythmia events with quizartinib were uncommon. Two (0.8%) patients receiving quizartinib experienced cardiac arrest with recorded ventricular fibrillation on ECG (one with fatal outcome), both in the setting of severe hypokalemia.

About QuANTUM-First
QuANTUM-First is a randomized, double-blind, placebo-controlled, global phase 3 study evaluating quizartinib in combination with standard induction and consolidation therapy, including HSCT, and as maintenance monotherapy, in adult patients aged 18-75 with newly diagnosed FLT3-ITD positive AML. Patients were randomized 1:1 to receive quizartinib or placebo combined with cytarabine and anthracycline induction and cytarabine consolidation chemotherapy followed by up to three years of treatment with single-agent maintenance.

The primary study endpoint was overall survival. Secondary endpoints include event-free survival, post-induction rates of complete remission (CR) and composite complete remission (CRc), and the percentage of patients who achieve CR or CRc with FLT3-ITD measurable residual disease negativity. Safety and pharmacokinetics, along with exploratory efficacy and biomarker endpoints including duration of CR were also evaluated.

QuANTUM-First enrolled 539 patients at 193 study sites in 26 countries across Asia, Europe, North America, Oceania and South America. For more information, visit ClinicalTrials.gov.

About FLT3-ITD Positive Acute Myeloid Leukemia
More than 474,500 new cases of leukemia were reported globally in 2020 with more than 311,500 deaths.1 AML accounts for 23.1% of total leukemia cases worldwide and is most common in adults.2,3 In Europe, approximately 18,000 people are diagnosed with AML each year and the five-year survival rate is reported at 17% for adult patients.4,5

A number of gene mutations have been identified in AML, and FLT3 (FMS-like tyrosine kinase 3) mutations are the most common.6 Approximately 80% of FLT3 mutations are FLT3-ITD mutations, which drive cancer growth and contribute to particularly unfavorable prognosis including increased risk of relapse and shorter overall survival.6,7 FLT3-ITD mutations occur in about 25% of all AML cases, with frequency reported as high as 30%.6,7

About Quizartinib
Quizartinib is an oral, highly potent type II FLT3 inhibitor that selectively targets FLT3-ITD mutations and has been specifically developed for patients with FLT3-ITD positive AML.6

Quizartinib is approved in the U.S. in combination with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy, for the treatment of adult patients with newly diagnosed AML that is FLT3-ITD positive as detected by an FDA-approved test. Quizartinib is not indicated as maintenance monotherapy following allogeneic hematopoietic stem cell transplantation (HSCT); improvement in overall survival with quizartinib in this setting has not been demonstrated.

Quizartinib also is approved in Japan for the treatment of AML that is FLT3-ITD mutation positive, including for use in combination with standard cytarabine and anthracycline induction and standard cytarabine consolidation chemotherapy and as maintenance monotherapy for adult patients with newly diagnosed FLT3-ITD positive AML, and as a monotherapy for relapsed/refractory AML that is FLT3-ITD positive as detected by an approved test. Quizartinib is an investigational medicine in all countries outside of Japan and the U.S.

About the Quizartinib Clinical Development Program
The quizartinib clinical development program includes a phase 1/2 trial in pediatric and young adult patients with relapsed/refractory FLT3-ITD positive AML in Europe and North America and several phase 1/2 combination studies as part of a strategic collaboration with The University of Texas MD Anderson Cancer Center.

On September 15, 2023 Scholar Rock (NASDAQ: SRRK; "The Company"), a Phase 3, clinical-stage biopharmaceutical company focused on the treatment of serious diseases in which protein growth factors play a fundamental role, reported that the company granted inducement equity awards covering an aggregate of 8,750 shares of its common stock to one newly hired employee, consisting of inducement stock options to purchase an aggregate of 5,000 shares of common stock and inducement restricted stock units, ("RSUs"), covering an aggregate of 3,750 shares of its common stock (Press release, Scholar Rock, SEP 15, 2023, View Source [SID1234635187]).

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The awards are subject to all terms and conditions and other provisions set forth in the Company’s 2022 Inducement Equity Plan ("The Plan") and the award agreements thereunder.

The Plan, which was adopted by the Company’s board of directors on June 16, 2022, is used exclusively for the grant of equity awards to individuals who were not previously employees of Scholar Rock, or following a bona fide period of non-employment, as an inducement material to such individuals entering into employment with Scholar Rock, pursuant to Nasdaq Listing Rule 5635(c)(4).

The options have an exercise price of $6.16, which is equal to the closing price of Scholar Rock’s common stock on September 11, 2023. The stock option award will vest with respect to 25% of the shares of common stock underlying the award on the first anniversary of the employee’s start date, and the remaining 75% of the shares of common stock underlying the Stock Option Award will vest in 12 equal quarterly installments thereafter. Vesting for RSUs will be in four equal annual installments. All vesting related to inducement awards is subject to the employees’ continuing service at the Company through the applicable vesting date.

On September 15, 2023 Harpoon Therapeutics, Inc. (Nasdaq: HARP), a clinical-stage immuno-oncology company developing novel T cell engagers, reported dosing of the first patients with small cell lung cancer (SCLC) in an ongoing Phase 1/2 trial of HPN328, a DLL3 targeting TriTAC, in combination with atezolizumab (Tecentriq) (Press release, Harpoon Therapeutics, SEP 15, 2023, View Source [SID1234635186]). Harpoon previously entered a Master Clinical Supply Agreement with F. Hoffmann-La Roche for the supply of atezolizumab. Under this agreement, Harpoon is the sponsor of the trial and Roche will supply atezolizumab. This announcement is being made in conjunction with Harpoon’s investor event, "DLL3 Market Opportunity and KOL Discussion of HPN328," held virtually and in person today in New York beginning at 8 a.m. ET.

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"Dosing the first patients in these combination cohorts for HPN328 with atezolizumab in patients with SCLC marks a significant milestone for this clinical program," said Luke Walker, M.D., Chief Medical Officer for Harpoon Therapeutics. "Building on the strength of our Phase 1 data, we remain committed to realizing the full potential of HPN328 as an important treatment option for patients with SCLC and other neuroendocrine tumors across early and late lines of therapy."

About the HPN328 + Atezolizumab Combination Cohort
Previously treated extensive stage SCLC patients enrolled in these combination cohorts will be dosed with HPN328 administered once every 2 weeks (Q2W) by IV infusion during each 28-day cycle. Atezolizumab will be administered once every 4 weeks (Q4W) by IV infusion on day 1 of each 28-day cycle. Primary outcome measures will include frequency and severity of treatment emergent adverse events (TEAEs), number and severity of dose limiting toxicities (DLTs), and pharmacokinetic parameters. Secondary outcome measures will include objective response rate (ORR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), and anti-drug antibody (ADA) formation. Enrollment in the combination cohorts has been initiated at the 12 mg Q2W HPN328 dose level, and escalation is planned per protocol dependent on data, with initial results from these combination cohorts expected in 2024. Separately, HPN328 interim Phase 1 monotherapy data will be presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) held on October 20-24, 2023.

Webcast Information for "DLL3 Market Opportunity and KOL Discussion of HPN328"

The webcast will begin at 8 a.m. ET and can be accessed using this link:
View Source;tp_key=667a2aef59
A live webcast and archived replay of the event will be accessible on the Investor Relations page of the Harpoon website at View Source

On September 15, 2023 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending approval of KEYTRUDA, Merck’s anti-PD-1 therapy, for the adjuvant treatment of adults with non-small cell lung cancer (NSCLC), who are at high risk of recurrence following complete resection and platinum-based chemotherapy (Press release, Merck & Co, SEP 15, 2023, View Source [SID1234635183]).

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The recommendation is based on results from the Phase 3 KEYNOTE-091 trial, in which KEYTRUDA demonstrated a statistically significant improvement in disease-free survival (DFS) in patients with NSCLC who are at high risk of recurrence (stage IB [T2a ≥4 centimeters], II or IIIA), and clinically meaningful results in the patients who received adjuvant chemotherapy. The CHMP’s recommendation will now be reviewed by the European Commission for marketing authorization in the European Union, and a final decision is expected in the fourth quarter of 2023.

"While KEYTRUDA is foundational in the treatment of metastatic non-small cell lung cancer, there continues to be an unmet need to help more patients with lung cancer in earlier stages of disease," said Dr. Gregory Lubiniecki, vice president, global clinical development, Merck Research Laboratories. "The CHMP’s positive recommendation brings us one step closer to providing a new adjuvant treatment option for patients in the European Union with earlier stages of non-small cell lung cancer, regardless of PD-L1 expression."

The KEYNOTE-091 trial, also known as EORTC-1416-LCG/ETOP-8-15 – PEARLS, was conducted in collaboration with the European Organisation for Research and Treatment of Cancer (EORTC) and the European Thoracic Oncology Platform (ETOP).

In January 2023, KEYTRUDA was approved, as a single agent, for adjuvant treatment following surgical resection and platinum-based chemotherapy for adult patients with stage IB (T2a ≥4 centimeters), II, or IIIA NSCLC in the U.S.

About lung cancer
Lung cancer is the leading cause of cancer death worldwide. In 2020 alone, there were more than 2.2 million new cases and 1.8 million deaths from lung cancer globally. Non-small cell lung cancer is the most common type of lung cancer, accounting for about 81% of all cases. In recent decades, the overall five-year survival rate for patients diagnosed with lung cancer increased from 11% to 15% on average across EU countries. Improved survival rates are due, in part, to earlier detection and screening, reduction in smoking, advances in diagnostic and surgical procedures, as well as the introduction of new therapies. Early detection and screening remain an important unmet need, as 44% of lung cancer cases are not found until they are advanced. Only 5.8% of people in the U.S. who are eligible were screened for lung cancer in 2021.

On September 15, 2023 Hoth Therapeutics, Inc. (NASDAQ: HOTH), a patient-focused biopharmaceutical company, reported that it has entered into a definitive agreement for the purchase and sale of 1,100,000 shares of its common stock (or common stock equivalents in lieu thereof) at a purchase price of $2.63 per share of common stock (or common stock equivalent in lieu thereof) in a registered direct offering priced at-the-market under Nasdaq rules (Press release, Hoth Therapeutics, SEP 15, 2023, View Source [SID1234635182]). In addition, in a concurrent private placement, Hoth will issue unregistered warrants to purchase up to 1,100,000 shares of its common stock. The warrants will have an exercise price of $2.505 per share and will be immediately exercisable upon issuance for a period of five years. The closing of the registered direct offering and the concurrent private placement is expected to occur on or about September 15, 2023, subject to the satisfaction of customary closing conditions.

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H.C. Wainwright & Co. is acting as the exclusive placement agent for the offering.

The gross proceeds to Hoth from the offering are expected to be approximately $2.89 million, before deducting the placement agent’s fees and other offering expenses payable by Hoth. Hoth intends to use the net proceeds from the offering for general working capital needs.

The shares of common stock (or common stock equivalents in lieu thereof) being offered in the registered direct offering (but not the warrants being in the concurrent private placement or the shares of common stock underlying such warrants) are being offered by Hoth pursuant to a "shelf" registration statement on Form S-3 (File No. 333-272620) previously filed with the Securities and Exchange Commission (the "SEC") on June 13, 2023 and declared effective by the SEC on June 16, 2023. The offering of the shares of common stock (or common stock equivalents in lieu thereof) in the registered direct offering is made only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement. A final prospectus supplement and accompanying prospectus relating to the registered direct offering will be filed with the SEC. Electronic copies of the final prospectus supplement and accompanying prospectus may be obtained, when available, on the SEC’s website at View Source or by contacting H.C. Wainwright & Co., LLC at 430 Park Avenue, 3rd Floor, New York, NY 10022, by phone at (212) 865-5711 or e-mail at [email protected].

The warrants described above are being issued in a concurrent private placement under Section 4(a)(2) of the Securities Act of 1933, as amended (the "Securities Act"), and Regulation D promulgated thereunder and, along with the shares of common stock underlying such warrants, have not been registered under the Securities Act, or applicable state securities laws. Accordingly, the warrants and underlying shares of common stock may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Securities Act and such applicable state securities laws.

This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.